D partials and weaks Flashcards
4 groups of altered D
- Weak D 2. Partial D 3. Del 4. Nonfunctional RhD
Weak D
SNPs affect the intracellular domain of the antigen- epitopes not different but ability to place protein in membrane is altered hence low level of expression
Weak D types 1-3
not at risk for making anti-D (90% of weak D types for European ancestry)
Most common Weak D type and mutation
Weak D type one Valine270Glycine
How many weak D types are there
135
Ceppelini affect
C in Trans, C on opposite haplotype to D weakens the expression of D, this occurs in r’ phenotype
General rule for antibody production in partial D’s
can make anti-D antibody when exposed. Most partial D’s are hybrid genes with a recombination of RhD and RhCE, some partials are due to multiple nucleotide changes
DVI new antigen
BARC antigen
Rhnull gene nomenclature
RHD*01N non-functioning RhD gene that do not encode full length polypeptide
Del
10-30% D negative Asians, antigen can only be detected by elution studies due to faulty transplantation into RBC membrane, due to multiple different RhD mutation. Most associated with r’ phenotype
DHAR population
european
Crawford population
<0.1% blacks
What phenotypes (2) can show strong reactive positive results with certain monoclonal reagents but are negative with others
Crawford and DHAR - both lack expression of ‘conventional’ D and can be sensitized to D
Elevated D:
Rare deletion phenotypes D- - D c -, Dcw- , increased expression of D; no/altered or weak expression of C/c, E/e antigens. Hybrid D antigen, RhCE portions being replaced by RhD gene
D negative percentages per population
W-15% B 8% A (<0.1%)
DHAR positive with what reagents?
Almost all anti-sera except Orthobioclone and polyclonal
Crawford positive with what reagents?
negative with all reagents except positive with gammaclone (albuclone?)
D negative in europeans
most common D negative is a deletion of entire gene- homozygous for this trait
D Psuedogene
in a.a. 37 b.p. insertion into RhD results in a premature stop codon, no functional protein made
DVI variant
can make anti-D this is a partial D, very severe HDFN. not detected on bench typically needs a weak D test in order to pick up. Most common partial D in europeans.
anti-D reagents composed of:
IgM anti-D to detect at IS, IgG anti-D to detect Weak D during weak D testing. “blended reagent”
anti-D column agglutionation
only contains IgM** cannot detect Weak D positive
Weak D types 11 and 15
have been shown to make anti-D when exposed. All other types (besides 1-3) we are unsure of the potential of alloimmunization.
African american two most common Partial D’s
DIIIa and DAR, both typically test strong positive with anti-D though they can be alloimmunized and often are not recognized as variants until they make the antibody.
percentage of hospitalized patients that make anti-D when exposed
30%
Requirement for hospitals providing Rh pos to Rh neg
AABB standards require that hospitals have a procedure for providing D negative patients with D positive blood and rhig as it’s not entirely without risk
Altered C phenotypes
Cw Cx both have nucleotide changes seen in approximately 2% europeans
Altered/partial C
JAHK and JAL african americans
Most common partial C
RhD*DIIIa-CE(4-7)-D hybrid. (also without final D) encodes exons 4-7 from CE gene onto RhD gene, however this does not encode D antigen, it encodes a partial C antigen on a D hybrid background. (Most common in a.a.’s 20% D negative a.a.’S have this and inherited with allele: r’s ces. Partial e antigen V- VS+) may be lacking hrb hrs
Rh null signature signs
stomatocytes- due to membrane instability
hrb and hrs
antigens that are high prevalence associated with partial e- can be produced in conjunction with DIII DAR (partial D’s)
Ce
rhi
ce
f
CE
RH22
cE
RH27
RHAG antigens
single a.a. substitution makes 4 amino acids: Duclos, Ola, DSLK, RHAG4
Proteins that make up Rh complex
RHAG, LW, Rh, GPA, Band3 Duffy, GPC/GPD
Rhnull-regulator type
regulator type- nucleotide changes in RHAG implying it’s role in insertion of RH into RBC membrane.
Rhnull-amorph
complete deletion of D gene as well as multiple mutations in RhCE
E,e, C, c HDFN
ANTI-c causes severe HDFN the other three are not typically associated with HDFN
antibodies associated with Rhnull
anti-Rh29 very high prevalence antigen
high prevalence antigens in Rh
hrs, hrb, HRb, Hr
Do companies have any responsibilities for the reaction to their reagent with partial D’s
FDA mandates the companies are required to list what their specific reagent reacts with, or may not react with. (DIV, DV, DVI)
HDFN D negative baby with positive DAT and mom has anti-D in serum
most likely due to ‘blocking affect’ all of mother’s anti-D is bound to fetal red cells therefore anti-sera anti-D cannot bind and appears negative, though actually positive. antibody must be removed with heat elution. increase to 45C can then test eluate for anti-D
